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Hdac1 and Hdac2 regulate the quiescent state and survival of hair-follicle mesenchymal niche

Author

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  • Hadas Sibony-Benyamini

    (Bar Ilan University)

  • Emil Aamar

    (Bar Ilan University)

  • David Enshell-Seijffers

    (Bar Ilan University)

Abstract

While cell division is essential for self-renewal and differentiation of stem cells and progenitors, dormancy is required to maintain the structure and function of the stem-cell niche. Here we use the hair follicle to show that during growth, the mesenchymal niche of the hair follicle, the dermal papilla (DP), is maintained quiescent by the activity of Hdac1 and Hdac2 in the DP that suppresses the expression of cell-cycle genes. Furthermore, Hdac1 and Hdac2 in the DP promote the survival of DP cells throughout the hair cycle. While during growth and regression this includes downregulation of p53 activity and the control of p53-independent programs, during quiescence, this predominantly involves p53-independent mechanisms. Remarkably, Hdac1 and Hdac2 in the DP during the growth phase also participate in orchestrating the hair cycle clock by maintaining physiological levels of Wnt signaling in the vicinity of the DP. Our findings not only provide insight into the molecular mechanism that sustains the function of the stem-cell niche in a persistently changing microenvironment, but also unveil that the same mechanism provides a molecular toolbox allowing the DP to affect and fine tune the microenvironment.

Suggested Citation

  • Hadas Sibony-Benyamini & Emil Aamar & David Enshell-Seijffers, 2023. "Hdac1 and Hdac2 regulate the quiescent state and survival of hair-follicle mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40573-7
    DOI: 10.1038/s41467-023-40573-7
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    References listed on IDEAS

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    1. Panteleimon Rompolas & Elizabeth R. Deschene & Giovanni Zito & David G. Gonzalez & Ichiko Saotome & Ann M. Haberman & Valentina Greco, 2012. "Live imaging of stem cell and progeny behaviour in physiological hair-follicle regeneration," Nature, Nature, vol. 487(7408), pages 496-499, July.
    2. Kailin R. Mesa & Panteleimon Rompolas & Giovanni Zito & Peggy Myung & Thomas Y. Sun & Samara Brown & David G. Gonzalez & Krastan B. Blagoev & Ann M. Haberman & Valentina Greco, 2015. "Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool," Nature, Nature, vol. 522(7554), pages 94-97, June.
    3. Ignacio Palmero & Cristina Pantoja & Manuel Serrano, 1998. "p19ARF links the tumour suppressor p53 to Ras," Nature, Nature, vol. 395(6698), pages 125-126, September.
    4. Sarina Harshuk-Shabso & Hila Dressler & Christof Niehrs & Emil Aamar & David Enshell-Seijffers, 2020. "Fgf and Wnt signaling interaction in the mesenchymal niche regulates the murine hair cycle clock," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    5. Maksim V. Plikus & Julie Ann Mayer & Damon de la Cruz & Ruth E. Baker & Philip K. Maini & Robert Maxson & Cheng-Ming Chuong, 2008. "Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration," Nature, Nature, vol. 451(7176), pages 340-344, January.
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